Previous studies have indicated that inhibitors of DNA synthesis and cell division can be isolated from various tissues. It has been shown that they have tissue but not species specificity. These studies are concerned with the isolation and characterization of an inhibitor of DNA synthesis and cell division from human placenta. The material has been semipurified and shown to be a macromolecule most likely a protein. It is active against fibroblast, lymphocytes, and epidermal cells. Purification of the material will be done with exchange chromatography, gel filtration, membrane sieving, and preparative acrylamide electrophoresis. The conditions of pH, ionic strength, temperature, and electrolyte content as well as cofactors necessary for stabilization will be investigated. The assay for activity will utilize the incorporation of H3-thymidine into the DNA of lymphocytes, fibroblasts, and epidermal cells maintained in culture. The analytical techniques for identifying the inhibitor will include electrophoresis, amino acid analysis, end group determination, ultracentrifugation and antibody production. Fetal tissues and adult tissues will be examined for the presence of the inhibitor. A variety of animal and human tissues will be examined for their responsiveness to the placental inhibitor in order to determine the specificity of the reaction. These studies will clarify the nature of the placental inhibitor and indicate if it consists of more than one component. This work will form the basis for future studies of mechanism of action.